A longitudinal treatment plan needs to be developed with the patient. The discussion should address disease prognosis
and treatment options, taking into account the costs,adverse effects,expected time for response, and monitoring requirements
of pharmacologic agents,in addition to the patient's preferences.
Expectations for treatment and potential barriers to carrying out the recommendations should be discussed. Patient education
is critical to engaging the patient in an effective partnership for managing the disease
The aggressiveness and timing of the treatment program require an assessment of prognosis. Poor prognosis is suggested
by earlier age of onset,high titer of RF,elevated ESR,and swelling of >20 joints.
Extra-articular manifestations of RA,including rheumatoid nodules, Sjogren's syndrome,episcleritis and scleritis, intestitial
lung disease, systemic vasculitis,and Felty's syndrome,indicate a worse prognosis. These manifestations may vary in severity
and significance.
Treatment of RA----Nonsteriodal anti-inflammatory drugs (NSAIDs). The initial drug treatment of RA usually involves the
use of NSAIDs to reduce joint pain and swelling and improve function. NSAIDs have analgestic and anti-inflammatory properties
but do not alter the course of the disease or prevent joint destruction.
Goal: Symtomatic relief of pain and swelling. Limitation: Unlikely to prevent damage. Factors for selecting drugs: Dosing
regimen, efficacy, tolerance, costs ,patient age,presence of comorbid disease(s), patient preferences and concurrent drugs.
Monitoring efficacy--Symptoms of active synovitis. Monitoring of toxicity is to be performed.
There are significant individual effects in efficacy among the many NSAIDs,and there are some differences
in the incidence of side effects. Salicylates are inexpensive, and blood levels may be measured to confirm that there
has been an adequate anti-inflammatory dose and to assess compliance. Analgesic effects of salicylates and NSAIDs are prompt
in onset, but reduction of inflammation may take up to 1-2 weeks or longer.
Patients with NSAID-induced GI intolerance or toxicity may require the concomitant use of GI-protective agents (misoprostal,cytotec
etc.). There are newer NSAIDs such as Vioxx and Celebrex--Cox-2 inhibitors available that are designed to lessen GI tolerance.
Disease-modifying anti-rheumatic drugs (DMARDs). All patients whose RA remains active despite adequate treatment with
NSAIDs are candidates for DMARD therapy. (NSAID and DMARD are used together). Active RA may lead to irreversible joint damage
even in the early months of the disease,while NSAIDs and glucocorsteriods may alleviate symptoms,joint damage may occur and
progress.
DMARDs have the potential to reduce or prevent joint damage, preserve joint integrity and function,and, ultimately:to
reduce the total cost of health care and maintain economic productivity of the patient with RA.
Goal: Remission or optimal control of inflammatory joint disease. Limitations: May not prevent damage in spite
of apparent clinical control-may not have lasting efficacy-may not be tolerated to toxicity.
Factors for selecting drugs Convenience and cost of medication and monitoring of toxicity-risk of adverse reactions,including
frequency and seriousnss.-physician estimate of efficacy and disease prognosis. Toxicity must be monitored.
Glucocorticoids: Low dose oral glucocorticoids ( <=10 mg predisone or equivalent) and local injections of glucocorticoids
are highly effective for relieving symptoms in patients with active RA. Low-dose gluco-corticoids appear to slow the
rate of of joint damage.
The adverse effects of systemic glucocorticoids,especially when taken in higher doses for extended periods of time,limit
their use,however. When administered by an experienced physician glucocorticoid injection of joints is relatively safe,and
effective.
Injecting one or a few of the most involved joints in a patient early in the course of RA may provide local,and
even systemic benefit. The effects are sometimes dramatic, but may be temporary. A patient who has flares in one
or more joints can be treated successfully by injection of the flaring joint or joints,without requiring a major change
in the prescribed regimen.
Low-dose oral glucocorticoids may benefit the patient during the period before a DMARD has gained its full effect and
when the disease is severe enough to affect the patient's function,sleep,or ability to work.
For patients receiving systemic glucocorticoids who exibit stable or improving disease,tapering of the doseage (slowly
and incrementally) and eventual discontinuation of the medication should be attempted ("bridge therapy").
Even if inflammation is successfully controlled or eliminated with medication, patients with chronic RA may be symptomatic
from joint damage. If,in spite of optimal medical treatment,the patient has unacceptable pain and/or limitation of function
because of structural damage,surgery should be considered. Surgery is not for everyone, however,and the decision should be
made after careful consideration by patient and doctor:
Joint replacement-- This is the most frequently performed surgery for RA,and it is done primarily to relieve pain and
improve or preserve joint function. Artificial joints are not always permanent and may eventually have to be replaced.This
may be a issue for younger people. Upgrade and research into superior longer-lasting implants is on-going.
Tendon recontruction: RA can damage and even rupture tendons,the tissues that attach muscle to bone.This surgery,which
is used most frequently on the hands,reconstructs the damaged tendon by attaching an intact tendon to it.This procedure can
help to restore function, especially if the tendon is completely ruptured.
Synovectomy: in this surgery,the doctor actually removes the inflamed synovial tissue. Synovectomy by itself is seldom
performed now because not all of the tissue can be removed,and it grows back Synovectomy is done as part of reconstructive
surgery,especially tendon reconstruction.
Essential component of management include:
1) Establishment of the diagnosis of RA (versus other forms of polyarthritis).
2) Systemic and regular evaluation of disease activity. (monitoring)
3) Patient education/rehabilitation interventions and initial treatment with NSAIDs.
4) Use of DMARDs. (early)
5) Possible use of local or low-dose oral glucocorticoids.
6) Minimization of the impact on the individuals's function.
7) Assessment of the adequacy of the treatment program and general health maintenance.
The course of rheumatoid arthritis cannot be predicted in a given patient. Several patterns have
been described:
*A spontaneous remission particularily in the seronegative patient (mild RA) within the first 24 months
of symptoms (less than 10%).
*Recurrent explosive attacks followed by periods of quiescence,most commonly in the early phases.
*The usual pattern of persistant and progressive disease that wanes and waxes in intensity.
*There is mild-prominent stiffness-moderate-severe RA patients.
*Some patients will have extra-articular features associated with the disease that can affect the whole
body.
*The pattern of disease activity,severity and disease progression will be individualized in most
patients -this also applies to medication and therapy.
Disability is higher among patients with RA with 60 % being unable to work 10 years after the onset
of disease. Recent studies have demonstrated an increased mortality in rheumatoid arthritis patients. Median life expectancy
was shortened an average of 7 years for men and 3 years for women compared to controlled populations in more than 5000 patients
with RA from four centres.
The mortality rate was two times greater than in the control population. Patients at risk for shortened survival are
those with with systemic extra-articular involvement,low functional capacity,low social-economic status,low education and
predisone use,according to the study.
Studies often have flaws-I have some reservations about social-economic-low-education factors.
Rheumatoid arthritis usually starts gradually,but it can start suddenly in some. You might feel tired and
achy,like you have the flu. Most people feel pain and stiffness in one or more joints,usually the hands,wrists,or feet. The
joints may not be swollen at the beginning but will probably start to swell within a couple of months.
The joints pain almost always occurs in symmetrical joints,i.e.,the same joints on both sides of the body.
E.G.,you might feel pain in both wrists or in the same finger on both hands. This is the usual case. Some people do not het
joint pain right away,they just feel stiff all over,especially when they get up in the morning. The stiffness usually lasts
1 hour or more,others say the stiffness never goes away.
Other patients feel achy and stiff,particularily in the hips and shoulders,and this may continue for weeks
or months before the joints start to swell-feel warm (inflammation ). This course occurs more in older patients and
may be confused with a disease called polymyalgia rheumatica.
Other people have swollen joints that are not painful at onset. There is much variation in the symptoms of
rheumatoid arthritis and that also applies to patient efficacy of medication. One drug will work wonders for one patient and
do nothing for another.
Side effects follow a similiar pattern in some patients. However,a symmetric painful series of
joints particularily in the hands,feet,and wrists is the most common presentation of this disease.
In some people,the joints are painful and swollen,then they get better,then worse again. RA can also,but very
rarely,be asymmetric,i.e.,it can occur in a joint on one side of the body but not in the other side corresponding joint on
the other side. Eventually,even in these people,the joints on the other side is also affected.-the disease becomes symmetric,the
typical course of rheumatoid arthritis.
It was traditionally taught that 70-80% of RA patients could be controlled with NSAIDs alone. These NSAIDs
were given on the false premise that most people with time will go into remission. Second-line drugs were considered "highly
toxic" and were reserved for those patients who could not be controlled by the first-line drugs. It is now,well established,that
spontaneous remission are not common and that early treatment with DMARDs is essential.
Dramatic changes have occurred in the treatment of RA and other inflammatory arthritis. Early aggressive treatment,the
continuous use of DMARDs and the use of combinations of DMARDs to eradicate inflammation have become the accepted standard
treatment. DMARDs can modify the natural course of rheumatic disease by preventing or delaying cartilage and bone destruction.
The effect of these agents is 2-fold by controlling joint inflammation,they provide symptomatic relief of
pain,swelling and stiffness,and by preventing cartilage and bone destruction,they reduce joint damage and subsequent disability.
The latter effect distinguishes this class of agents from other drugs such as NSAIDs.
The importance of treating RA early cannot be overemphasized. There is a window of opportunity for good control
of the disease and prevention of joint damage early in the course of the illness. Irreversible erosion can be seen
on x-ray films within the first 1-2 years after the onset of the disease,and even earlier using magnetic resonance imaging.
Delays in treatment as short as 8-9 months have been associated with significantly damage and disability at 3 years and 5
years of follow-up.
Current recommendations include starting DMARD therapy as soon as the diagnosis of RA has been established.
This means after 6 weeks of inflammation despite treatment with anti-inflammatory drugs. The aim of therapy is no longer simply
to control the symptoms at a level of comfort that is satisfactory to the patient but also to eradicate inflammation,and thus
have a greater impact on the associated disability.
More aggressive therapy means continuous use of DMARDs, increasing the doseage to maximum tolerated or recommended
until miminal or no inflammation is achieved,switching to a different DMARD if no benefit is obtained after a trial
at the maximum dose for an appropriate duration,and using combination therapy. Although DMARDs are potentially toxic,,their
skillful use by a experienced clinician can help prevent problems. The incidence of serious side effects in long-term studies
is rare.
Consultation with a rheumatologist is desirable before initiating DMARD treatment. It is important to have
a definite diagnosis of RA before beginning DMARD therapy to avoid exposing patients to the risk of serious side effects for
a benign transient arthritis.
The trend toward earlier and more aggressive treatment is not limited to RA. It has also shown to affect the
prognosis of other rheumatic diseases,such as lupus nephritis,polymyositis,dermatomyositis and vasculitides.
Because a respose may not be observed for up to several months after DMARD therapy is started,it is important
to offer support to patients during the waiting period. One or more intra-articular corticosteriod injections may be beneficial
in alleviating the symptoms of joint inflammation. Alternatively low-dose predisone administered orally may be prescribed
as "bridging therapy" until the effects of the second-line agent is felt.
Exercise helps lessen the symptoms of RA and can make you feel better overall. Appropriate and moderate stretching
and strengthening will help relieve the pain,and keep the muscles,and tendons around the affected joint flexibile,and strong.
Low impact exercises like swimming, walking,water aerobics,and perhaps stationary bicycling (if the knee is affected
consult your doctor) can all reduce pain while maintaining strength, flexibility,and cardiovascular function
Physical therapists (preferably trained in rheumatic disease treatment) can teach you other techniques to
manage the pain,and restore joint motion,and muscle strength. With the aid of properly trained occupational therapists,they
can assist the patient in maintaining optimal function at work,in the home,and during leisure activities. There
are also nurses specifically trained in rheumatic diseases.
Patients may be referred to physiotheraphy and occupational therapy for treatments such as icing,the applying
of wax and ultrasonography to reduce the symptom of inflammation. They may be referred to the Arthritis Self-Management Program.or
other educational programs, offered by the Arthritis Society of Canada ( http://www.arthritis.ca/) and others,to help them understand their disease and,thus,improve their ability to cope with symptoms. Patients must be
made aware of the need for monitoring. The incidence of serious side effects is markedly reduced with regular monitoring,because
adverse effects are more likely to be discovered before serious serious or irreversible consequences arise.
Despite the long list of side effects which intimidates patients,long-term series of RA patients treated with
DMARDs have found that serious side effects are rare.
When counselling a patient who express concern about potential side effects,it is also important to remind
him or her of the consequences of the alternative, doing nothing will result in irreversible disability,progressive joint
damage and premature death. Drugs such as methotrexate and cyclosporine, which are used in cancer therapy and transplant therapy
respectively,are used in lower doses for RA.and the incidense of adverse side effects is lower. Persistence in the use of
DMARD is of great importance.
DMARDs are used to treat incurable chronic diseases when treatment will be lifelong and the number of options
is limited. Typically a patient with RA will use a succession of DMARDs over the years. After an initial response,a drug is
often eventually discontinued,either because of adverse side effects or loss of effect.
To ensure the best result,it is important to give each drug a full trial, namely,the maximum dose for sufficient
time,before declaring a drug is not efficacious. There are a number of strategies for dealing with common side effects.
The use of combination DMARDs is now widely practised,Some physicians advocate the use of combination therapy
at the onset of disease early control,with a subsequent gradual withdrawal of therapy,as necessary to maintain control. Others
prefer the opposite strategy successively adding DMARDs to agents to which the patient has shown a partial response. Proponents
of the latter view,believe it prevents unnecessary exposure to potentially toxic drugs of patients who may respond to single
therapy
Commonly used combinations include hydroxychloroquine with most DMARDs,especially methotrexate. or intramuscular
gold,sulfasalazine and methotrexate with or without hydroxychloroquine,and cyclosporine and methotrexate.
The most accurate and most often used measurement of inflammation is the sedimintation rate or "sed rate".This
test is based on how quickly red blood cells settle at the bottom of the test tube.The ESR is useful in differentiating
RA from other types of arthritis. If your joints are very swollen your doctor may take a small sample from the swollen joint.Normal
synovial fluid is clear,thick and oily,it becomes cloudy because it is infiltered with usually white blood cells and debris
Baseline laboratory evaluations should include complete blood count (CBC), platelet count,chemistery profile,RF
measurement,and measurement of ESR or CRP. Evaluation of renal and hepatic function is necessary since many antirheumatic
agents have renal or hepatic toxicity and may be contraindicated if these organs are impaired.
There's a wide variety of topical creams and gels available that provide temporarily pain relief-including
a prescription cream made from the active ingredient (capsaicin) in hot chili peppers. Some creams contain the active ingrediant
(acrtylsalicylic acid) in ASA,which is absorbed through your skin and should be factored into your total daily dose if you're
taking ASA or ibuprofen in tablet form. Since it's difficult to calculate how much ASA you've absorbed into a cream,try to
avoid using a cream and tablets on the same day. And keep in mind that all such creams are for pain relief only,they aren't
effective as NSAIDs.
The majority of creams and gels (and liniments and poulticies)are counter irritants,which work by pitting
one pain against another, inducing the body to lower its sensitivity. Applied to a painful joint,they produce a temporary
local reaction that may cause skin irritation,mild swelling or a temperature change-and a lessening of pain.Most such counterirritants
use heat or cold to'distract' the brain from recognizing the signal from the pain source by amplifying the nerve signals recieved
by your brain's pain centres. Overwelmed by the influx of chemical messages,the brain temporarily'switches' them off,thus
providing pain relief.
According to a 1995 ,November issue of Letters,at the University of Berkeley,clinical studies into capsaicin's
use have been small and short-term,and not much is known about the effect of long-term use. Still,they note that many people
find capsaicin helps. 'As the package direction should say,you need to use the cream 3 or 4 times a day,and you may not notice
much improvement until you've applied the cream for a week or more. Many people can't tolerate it-skin becomes irritated.
Never use the cream under a bandage,and don't get it into your eyes. or an open cut.
For some people,rubbing one of these salves on a arthritic joint is as effective as the pain relief they experience
from NSAIDs. Capsaicin,the alkaloid that gives chili peppers their fire,has been recruited as a counterirritant. Nonprescription
salves or lotions,such as Zostrix,Capzasin-P and Capsin contains 0.025 to 0.25 % capsaicin, through a tube of cream may contain
as much pure capsaicin as hundreds of chili peppers. While such creams generate a feeling of warmth on the skin,their effect
is muted enough that you can apply the treatment several times a day.
Some promising combinations include:
1) Methotrexate (MTX) and Sulfasalazine (SSZ) and Hydroxychloroquine.(HCQ)
2) MTX and Intramuscular Gold .
3) MTX and Etanercept. (Enbrel )
4) MTX and Leflunomide ( Arava )
5) MTX and Infliximab. ( Remicade )
6) MTX and Cyclosporin has been tried ,but due to higher toxicity of cyclosporin it is not used commonly,today.
7) MTX and Arava ( Leflunomide ) might not work for everyone. Monitoring and selection will vary due to differences
in patient efficacy. Methotrexate has become the gold standard in North America. It promises early onset of action,usually
within 4 to 6 weeks. MTX is usually given as tablets,but can be given subcutaneously.
The effective weekly dose for a patient may be low as two 2.5 mg tablets,or as high as ten. The average is 5 tablets
(12.5mg.) once a week. Because the effective dose range is so wide,its best to start low (3 tablets / week). and only slowly
increase the dose by one tablet each time. changes in dose should occur no more often than every 3 weeks;once a month is the
usual. It is unusual to notice a good response at a fairly low dose at first,but then to require a higher dose
later on to maintain that response. a complete blood count (hemoglobin,white cell and platelet counts ) is usually done every
2 weeks until the final dose is selected,then every 4 to 6 weeks Liver function test may be performed,depending on the patient
situation. Some patients claim better response with the injection procedure with less side effects. NSAIDs don't
interact with MTX when MTX is taken in the doses recommmended; however,sulfa-containg antibiotics increase the risk of side
effects and should be avoided. Side effects are ofen dealt with by decreasing the dose or temporarily stopping MTX and then
restarting it. Gold has the potential of disease suppression.,but it is more toxic The refular dose is (50 mg./weekly).
To make sure the patient isn't sensitive to gold,two small test doses of aurothiomalate are given,one week apart. The practise
in the past was to do this,once a week,until 1,000 mg. had been given,and some doctors may still do this. If the patient is
no better,then they try another drug The major disadavantage include the need to visit the doctor each week,the
longer time for efficacy (12 to 20 weeks), Blood tests and urine tests are usually done prior to injection. Twenty weeks is
a long time to wait to see if the drug works or not. If it does not work,it is valuable "wasted time" w.r.t. to the ongoing
disease process. Azathioprine is taken daily. The initial dose is one tablet (50 mg) and later the dose is adjusted
according to the patient's weight. Later,if the patient has done well,the dose can be reduced without losing the effect. Once
a regular dose has been settled on complete blood counts (CBC) are needed less frequently than with mtx and gold,but it should
still be checked at least every 3 months. Sulfazaline is used more in Europe. The British rank it somewhere near
intramuscular gold. Its safety profile is excellent. It takes action in 2 to 3 months There are some conflicting
reports as to whether SSZ is useful in some of the seronegative arthritis cases, PA and AS. SSZ should be started with a low
dose and gradually built up. Start with one tablet (500 mg) a day for a week,then increase the daily dose by one tablet each
week until, by the fourth week the patient is taking two tablets twice a day, there are other variations to this schedule. Hydroxychloroquine
HCQ) is considered to be much weaker than almost all the other DMARDs(plaquenil). It's safety profile is excellent It
takes effect in 3 to 6 months ,but its long-term benifit is not so good as the others. In the case of severe RA,six months
is a long time to wait,and find the drug ineffective. It's very important to get a annual eye check up. The maximum
daily dose is 400 mg-calculated w.r.t. bodyweight--200 mg/twice/daily. Auranofin-oral gold has been proven to
be a disappointment. There is little flexibility in the dose of auranofin- one 3 mg. tablet twice a day. A complete CBC and
urinalysis /monthly. D-penicillamine and cyclosporin is not commonly used today . With the many alternative,including
the newer biologics the two are on the "back-burner" but when every thing else fails,they are available-they have higher toxicity
levels,and hard to control,at times
The development of genetically engineered biologic agents that selectively block cytokines (anticytokine therapy) in
the short term,represents a major advance in the treatment of RA. Etanercept is a recombinant soluable TNF-fc fusion
protein,and infliximab is a chimeric (mouse-human ) anti-TNF monoclono antibody.
Infliximab is currently recommended for use only with concomitant MTX therapy. MTX may be used with etanercept or used
alone. Several randomized trials have demonstrated that patients with etanercept alone or with infliximab plus MTX have less
radiographic progression after 1 year rhan patients treated with MTX alone. In the trial with patients made up of early RA
patients,the symptoms and signs of RA improved more rapidly over the first 6 months,with compareable efficacy of the two agents
at 12 months.
The ACR guidlines for monitoring liver toxicity in patients recieving MTX is that a liver biopsy should be performed
in patients who develop abnormal findindings on liver function studies,that persist during treatment or upon discontinuing
the drug. Liver toxicity with MTX is rare.
Although data from randomized trials have not shown an increased frequency of adverse effects,such as infections or malignancies,for
either anti-TNF agent,concerns about the short-term and long-term safety of these agents continue. Enbrel was recently given
a 5 year safety approval in clinical trials.
Clinical trials have demonstrated the efficacy of infliximab and etanercept in improving clinical symptoms and signs
in patients with RA,according to the ACR 20,50,and ACR 70 improvement criteria. Patients with early active RA and those that
had failed previous conventional therapy showed improvements. Anti-TNF agents should be used with caution in patients susceptible
to infection or a history of T.B.,should be avoided in patients with significant chronic infections and should be discontinued,temporarily
in all patients with acute infection
Postmarketing surveillance has yielded reports of septis,tuberculosis.a typical mycobacterial infections,but it not common.
At this time there appears to be no need of routine laboratory testing. Not all patients will respond to TNF therapy. The
main disadavantage is high cost and parental administration.
Minocycline have shown efficacy in certain early,milder type RA patients. Surprisingly it showed efficacy in a subset
of patients who were positive for the HLA shared epitope (HLA-DR4+)(--A.S.) conclusion is further testing should be done on
tetracyclines.
Intramuscular gold treatment is effective,but injections are required every week for 22 weeks before less-frequent
maintaince dose is started. Oral gold althought more convenient,has proved less efficacious and is not commonly used.
Cyclosporine is beneficial and has short-term efficacy to that of D-Pen (not used frequently). the use of cyclosporine,however,has
been limited by its toxicity,expecially hypertension and dose-related renal function 20 %loss of renal function appears to
be reversible for renal function loss,but not entirely. Dose calculation to avoid renal toxicity is more critical with cyclosporine
than with any other DMARD. Cyclosporine plus MTX was found to be more effective than MTX alone but long-term follow up revealed
the development of hypertension and elevated creatinine levels
Low-dose oral glucocorticoids (<10 mg of prednisone daily,or the equivalent) and local injections of glucocortoids
are highly effective for relieving symptoms in patients with active RA. A patient disabled by active polyarthritis may
experience marked and rapid improvement in functional status within a matter of a short period. Frequently,disabling synovitis
recurs when steriods are discontinued,even in patients who are receiving combination therapy. However, many patients are functionally
dependent on steriods and continue them long-term.
Recent evidence suggest that low-dose glucocorticoids slow the rate of joint damage and appear to have disease-modifying
potential Joint damage may increase on discontinuation, Previously it was thought they did nothing to stop disese progression.
The benefits of low-dose glucocorticoids,should always be weighed against their adverse effects which are well documented
elsewhere.
Because of its favourable efficacy and toxicity profile,low cost and established track record in the treatment
of RA MTX has become the standard by which new DMARDs are evaluated.
More recent (1999 ) randomized clinical trials have established the efficacy of MTX in RA, particularily in patients
with more severe disease. Longitudal observational studies and randomized controlled trials show that MTX retards the progression
of radiographic erosions.
Observational studies indicate that more than 50 % of patients who take MTX continue the drug beyond 3 years,which is
longer than any other DMARD. RA patients taking MTX are more likely to discontinue treatment because of adverse reactions
than because of lack of efficacy.
Stomatitis,nausea,diarrhea,and perhaps alopecia caused by MTX may decrease with concomittant folic acid or folinic acid
treatment without significant loss of efficacy. Relative contraindications for MTX therapy are pre existing liver disease,renal
impairement,significant lung disease,or alcohol abuse.
Since the most frequent adverse reaction in MTX is elavation of liver enzyme levels,their function must be monitored,but
the risk of liver toxicity is very low
Clinical trials have established leflunomide as an alternate to MTX as monotherapy,especially for patients who cannot
tolerate MTX The reduction in RA disease activity and in the rate of radiologic progression achieved by leflunomide
appears to be equivalent to tht of a modest dose of MTX. Leflunomide is also used in combination therapy with MTX,in the absence
of a complete clinical response with full dose MTX.
Five percent of patients recieving leflunomide and up to 60 % of patients recieving MTX plus lefunomide have elevated
liver enzyme levels
Also,refer to Leflunomide or Arava,Enbrel Remicade,Glucosteriods,NSAIDs and DMARDs articles on site,for more information.
Conventional treatment with a single DMARD often fails to adequately control clinical symptoms or to prevent disease
progression As a result rheumatologists are increasingly prescribing combination DMARD therapy. Controversy remains
whether to initiate this type of therapy in a sequential "step-up" approach in patients with persistent active disease in
whom single agents have failed or whether to initiate combination therapy early in the disease course and then apply a "step-down"
approach once adequate disease control is attained. In either case rheumatology referrel is strongly recommended,when considering
this route.
Since DMARDs control rather then cure RA,the management of RA is an iterative process and patients should be periodically
reassessed for evidence of disease or limitation of function with significant alteration of joint anatomy. Reconstructive
surgery can be done at any point in the course of RA.
Some patients have resistant disease and experience a progressive course despite exhaustive trials of DMARDs,whether
used alone or in combination. At each followup visit the physician must asess whether the disease is active or inactive. Symptoms
of inflammatory (as contrasted with mechanical ) joint disease,which includes prolonged morning stiffness,duration of fatigue,and
active joint synovitis on joint examination,indicate active disease and necessitate consideration of changing the treatment
regimen
Occassionally,findings of the joint examinations alone may not adequately reflect disease activity and structural damage.therefore,periodic
measurements of the ESR and CRP level and functional status as well as radiographic examinations of involved joints should
be performed.
Functional status may be determined by questionnaires such as the Arhtritis Impact Measurement Scales or the Health
Assessment Questionnaire. It is important to determine whether a decline in function is the result of inflammation,mechanical
damage or both,treatment strategies will differ. accordingly.
The American College of Rheumatology (ACR) has developed criterias for defining improvement and clinical remission in
RA. These criteria is accepted world-wide in rheumatology circles.
People living with RA will need to become more familiar with the treatment regimen,know when therapy is working and when
it is not. Familiarize themselves with side effects so that when they occur,intelligently inform their physicians as to change
of dose or medication to ensure safety,health,and success of the whole treatment and managment process.
Instruction in joint protection,conservation of energy,and a home program of joint range of motion and strengthenining
exercises are important in achieving the treatment goal of maintaining joint function. Occupational therapy and
physical therapy may help the patient who is compromised in activities of daily living.
Regular participation in dynamic and even aerobic conditioning programs improves joint mobility,muscle strength,aerobic
fitness and function and psychological well being without increasing fatigue or joint symptoms.
If complete remission is not achieved, (rare )the management goals are to control disease activity,alleviate pain,maintain
function for activities of daily living and work,and maximize function for activities of daily living living and work and
maximize quality of life.
Achieving these goals challenges the skill of the rheumatologist to determine the most efficacious combination of pharmacologic
therapy,which may include NSAID,DMARD(s),low-dose predisone,local injection of glucocortoid, rehabilitation support and analgesics.
Given the chronic waxing and waning course of RA,a longitudal treatment plan needs to be developed and the patient
should be involved in the treatment plan The discussion should include disease progression,prognosis and treatment options,taking
into account the cost,adverse risk factors and comorbid conditions monitoring disease activity (i.e., ongoing disease activity
after 3 months of maximum therapy ),or progressive joint damage require consideration of significant changes in the DMARD
regimen.
If disease activity is confined to one or a few joints,then local glucocortoid injection may help. For patients with
severe symptoms,systemic glucocorticoids may need to be initiated,or the dosage may need to be increased,for a short period
of time.
Active joint disease may impair physical activity. Therefore,consultation with a physical therapist,occupational therapist
and /or nurse trained in rheumatic diseases may be necessary
Periods of rest,job modification,time off from work,changes in occupation or termination of of work may be necessary
Reconstructive surgery should be considered for patients with end-stage joint damage that is causing unacceptable pain or
mobility problems.
The initial evaluation of the patient with RA should document symptoms of active disease (i.e. presence of joint pain,duration
of morning stiffness,degree of fatigue ) functional status,objective evidence of diseae activity (i.e., synovitis, as assessed
by tender swollen joint counts and the ESR or CRP level )mechanical joint problems (i.e.,loss of motion, cripitus, instability,and/or
deformity ) malalignment,the presence of extraarticular disease,and the presense of radiographic damage.
The presence of comorbid conditions should also be assessed. The patient's and physician's global assessments of disease
activity and a quantitative assessment of pain using a analog scale or other validated measure of function or quality of life
are useful parameters to follow during the course of the disease.
The baseline laboratory evaluations should include a complete blood cell count (with white blood cell differential and
platelet counts ),rheumatoid factor (RF) measurement,and measurement of ESR or CRP
Evaluation of renal and hepatic function is necessary,since many antirheumatic drugs cause renal or hepatic toxicity,and
may be contraindictated if these organs are impaired.
Since the hands and feet are so frequently involved in RA,radiographs of these joints as well as other affected joints
establish a baseline for future assessment of structural damage. Arresting and preventing structural damage is a primary goal
of therapy.and radiographic studies of major involved joints may be neded periodically
Selection of the treatment regimen requires an assessment of prognosis. Poor prognosis is suggested by earlier age of
disease onset,higher titer of RF,elevated ESR,and swelling of > 20 joints, Extraarticular manifestations of RA such as
rheumatoid nodules,Sjogren's syndrome,episcleritis and scleritis, interstitial lung disease,pericardial involvement,systemic
vasculitis and Felty's syndrome,may indicate a worse prognosis,but they have not ben widely adopted for clinical practice.
The ACR criteria for 20 % clinical improvement (the ACR 20) requires a 20 % improvement in the tender and swollen joint
count,as well as a 20 % improvement in 3 of the following 5 parameters:
1) Patient's global assessment.
2) Physician's global assessment.
3) Patient's assessment of pain.
4) Patient assessment of degree of disability.
5) Patient assessment level of acute-phase reactant
These criteria have been expanded to include criteria for 50 % improvement measures (i.e. ACR 50,ACR 70 )> Other criteria
such as the Paulus criteria have also been employed. More recently,radiographic progression (e.g.,the Sharp Score) has been
utilized as a outcome measure.
Start by trying to find out where the individual who has rheumatoid arthritis is with the particular illness. Different
things affect people in different ways. Some people may be very anxious about the future and be coping with the present very
well. Others may have difficulty even thinking about how to get up in the morning and proceed with their day. Often start
with where the patient is.
The initial thing is try to find out is whether they have support from their husband, wife, or other family members.
If they're employed, does their boss understand what's going on with them? People need a sense that this illness is not going
to isolate them. They need to be understood and have a feeling that other people care about them.
Getting support from family members and employers is very important. Oftentimes, feeling understood gratifies people
so much - they feel like other people care about them. It's often very important that they discuss the frustration and the
depression with their primary physician. The doctor may suggest a referral, so they can have an opportunity to really pour
their heart out about what's troubling them and what they're frightened of.
A psychiatrist,may suggest the use of antidepressant medication, though not necessarily right away. This often can be
quite helpful in lifting someone's mood and also can be helpful in terms of pain control even though it doesn't necessarily
do anything for the underlying arthritis process.
Not everyone needs a antidepressent,it depends on their coping skills. It depends on what their previous history
has been. If you have someone who has never been ill and all of a sudden has this diagnosis mentioned to them, the way that
they react to it will often reflect how they've dealt with other traumas in their life. If there is someone who has had multiple
illnesses, this additional illness can often give them an overwhelming sense of "What's going to happen to me?" and a complete
loss of control.
People like to feel like they're in control of themselves and in control of their health. When this starts to be preyed
upon, everyone feels a little bit of loss of self and somewhat of a loss of self-esteem. But we're talking about degrees here.
Depression and anger go hand-in-hand, as we all know. What do you tell a person who's living with rheumatoid arthritis
and who's frustrated with their inability to do the simple things that they used to be able to do?
Number one,try and empathize with them about how difficult that must be. Number two,tell them express themselves, how
angry they're feeling, even if they tell the therapist they're not angry. The therapist try to get to the point where they
understand that it's very normal to be angry, and they don't need to be afraid of their anger or feel guilty about their anger.
The therapist then work with them on how they're going to begin to get some of their expectations met and how they're
going to go on in life with a more positive focus rather than being so consumed with the idea that this disease is going to
take everything away from them. "It's very normal to be angry. Patient's are encouraged to get involved in learning
about their illness and in learning about good health in general."
As somebody coping with diabetes, which is another long-term chronic condition, sometimes it's not the disease that’s
the problem, it's the stress of coping with the disease. It always depends on the degree of involvement and how much
rheumatoid arthritis takes away from a person's everyday functioning. It is helpful is to get people involved with other rheumatoid
arthritis patients so that they hear that their complaints are similar to other patients struggling with the illness. Try
to encourage patients to do as many things as possible that they like to do and things that they used to do.
Patients need encouragement to get involved in learning about their illness and in learning about good health in general.
There are a lot of things like exercise and proper diet which we hear a lot about today that really do make some sense
for people who don't have a particular illness. But especially if you have a chronic illness, that's something that you have
to watch. The more you can help a person focus on the positive things about their life, the better they're going to be able
to tolerate having this particular illness
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